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Z Q Ma

Publications and source records attributed to Z Q Ma.

25 records · Page 2Linked to original sources
PubMed1993

Activated estrogen receptor mediates growth arrest and differentiation of a neuroblastoma cell line.

Several reports demonstrate estrogen receptor involvement in specific brain functions. In addition, estrogen receptors are expressed at early stages of brain development, suggesting that estrogens or related molecules may play an instructive role in the differentiation of specific brain areas. The lack of model systems in which these phenomena could be studied prompted us to develop a neuroblastoma cell line expressing the estrogen receptor. The cell line expresses the hormone receptor at levels compatible with a physiological activity. The activated estrogen receptor is capable of blocking proliferation of the cells without exerting toxic effects. Following growth arrest, the cells display a neuron-like morphology and express tau and synaptophysin, two proteins synthesized in differentiating neurons. The cell line generated will provide a valuable model system for molecular and biochemical studies of the activity of estrogens in neural-derived cells.

Cell Differentiation↗
PubMed1993

Estrogen modulation of catecholamine synthesis and monoamine oxidase A activity in the human neuroblastoma cell line SK-ER3.

In order to assess the neuronal-like properties of a human neuroblastoma cell line obtained by stable transfection of the estrogen receptor (SK-ER3) a series of quantitative measurements of the activity of two neurotransmitter-related enzymes: tyrosine hydroxylase (TH) and monamine oxidase (MAO), and of catecholamine concentrations were performed. When compared to the parental SK-N-BE cell line, the stably transfected SK-ER3 cells show a more pronounced dopaminergic phenotype. The immunoreactivity to a TH antibody is in fact increased and the ratio between dopamine and noradrenaline concentrations is elevated. Treatment with estradiol further enhances the expression of this phenotype. Interestingly, in the transfected cell line MAO-A activity is decreased and further reduced by estrogen treatment. This finding substantiated by previous reports indicates that our model system might represent an interesting tool for the study of the pharmacological treatments of estrogen-induced pathological responses of nervous cells.

Bucladesine↗
PubMedDate not supplied

Suppression of gene expression by tethering KRAB domain to promoter of ER target genes.

Estrogens play an important role in the development and progression of breast cancer. Although estrogen antagonist treatment often results in the arrest or remission of breast cancer growth, most breast cancers recur and become resistant to estrogen ablative therapy. The molecular mechanisms underlying these actions remain largely undefined. It is hypothesized that tumor cells of an advanced stage may develop compensatory pathways to stimulate the expression of estrogen receptor (ER) target genes or downstream events, independent of estrogen action. In this study, we developed a chimeric repressor to turn off ER target genes with the aim of directly investigating the role of ER target genes in tumor progression. The chimeric repressor contains the ER DNA-binding domain that recognizes estrogen response elements (EREs), a Krupple-associated box (KRAB) repressor domain which silences target genes when tethered to their promoter regions and a truncated progesterone ligand-binding domain which responds only to the exogenous synthetic ligand, RU486. The ability of the chimeric repressor to block ER mediated transcription was assessed in transient transfection assays. ER-induced reporter activity was inhibited by the repressor in a dose-dependent manner, with the maximum effect of more than 80% reduction. The inhibitory activity of the chimeric repressor was tightly under the control of RU486. Effective suppression by the repressor on the natural promoter of ER target gene, complement factor 3 (C3), was also observed. The inhibitory activity was specific to ER, since the repressor has no effect on other nuclear receptor systems tested. Furthermore, the repressor could inhibit the 4-hydroxy-tamoxifen (4OH-T)-induced ER activity. Taken together, our results demonstrate that the inducible repressor we have designed could specifically inhibit ER target gene expression in response to an exogenous synthetic ligand. This repressor will provide a useful tool to study the role of ER target genes in breast cancer progression and it may be potentially useful for gene therapy of breast cancer.

Base Sequence↗